Pharm: Drug Approval Process Flashcards
Assemble in correct order the timeline for drug approval, including the component parts and major “milestones”.
- R&D, in vitro and animal testing
- Get IND from FDA; clinical testing (in humans)
- Submit NDA to FDA–includes lots of documents, evidence, and fee
- Receive marketing approval
- Conduct marketing and post-market surveillance
Discuss the types and purpose of preclinical studies used in selecting “candidate” molecules to move forward to clinical trials.
- Modeling: pharmacometrics
- In vitro: assays to determine solubility, absorption, metabolism, receptor interaction
- In vivo (animals): toxicity, including acute, sub-acute, chronic, reproductive, carcinogenicity, mutagenicity, investigative toxicity
What is the basic design and purpose of Phase I clinical trials?
10-15 healthy volunteers or terminal cancer patients; goal is to determine the mean tolerable dose; starts from lower dose than animals
What is the basic design and purpose of Phase II clinical trials?
100-300 patients enrolled; begin with MTD from phase I and vary the dosing regimen to determine the drug’s effectiveness and toxicity level; the active non-toxic drugs move on to phase III
What is the basic design and purpose of Phase III clinical trials?
involves several hundred patients; usually designed in a randomized controlled, double blind fashion; goal is to show increased efficacy over established treatment or palcebo
What is the basic design and purpose of Phase IV clinical trials?
post-market surveillance to define drug activity “in the real world”; this may reveal rare side effects/AEs–and if drug toxicity is indeed defined FDA may withdraw the drug from the market
Rationalize the necessity for placebo arms in phase III trials.
The placebo effect is REAL; so you have to see if this new drug actually works, or if people just think it works because it’s a new drug
Explain the role of pharmacometrics in the drug approval process.
using computer programs to model the quantitative understanding of drug dose/exposure and response; uses information from known target/receptor interaction in order to predict the effectiveness and optimal dose of a new candidate drug; can also help improve trial design by gaining insight into prior failures
Describe the importance of the post-approval vigilance system (Phase IV review) and how reporting is conducted.
important because it can identify rare side effects/toxicities not seen in the limited trial population; reporting is via Medwatch and mandatory for death or serious injury, voluntary for other AEs/product problems
Discuss the purpose of legislation governing accelerated drug approval and abbreviated new drug applications, and describe the modified process each of these applications entails.
In order to bring drugs to market faster, the Drug Price Competition and Patent Restoration Act (1984) made accelerated and abbreviated NDAs:
- Accelerated = approval for drugs to treat serious or life-threatening illnesses based on surrogate endpoints that were considered reasonably likely to predict clinical benefit
- Abbreviated = FDA can approve generic drug versions without duplicating clinical trial, provided they demonstrate bioequivalence
What is the legislation governing schedule drugs and and what are the prescribing restrictions within the various schedules?
Legislation came through the COntrolled Substances Act (1970); established the DEA and placed all controlled substances into one of five schedules:
- C-I = highest abuse potential
- C-V = least abuse potential
- No one can prescribe C-I (research only); signature required and no refills for C-II; limited refills C-III/IV; OTC in some states for C-V
Explain the emerging requirements regarding drug labeling based upon pharmacogenomic considerations.
because of known genetic polymorphisms affecting drug transport, metabolism, and action on the target, FDA now recommends including pharmacogenomic information in the labeling that will indicate what effect genotype may have on phenotype and helps guide how to determine the effects of that drug on that patient and/or how to adjust the dose
There are 3 types of ads that may be run about drugs. Describe them and their limitations.
- Product Claim - include name, FDA-approved use, significant risks, balanced description of risks and benefits
- Reminder Ads - give name but not uses; can’t say how it works or how well, can’t say anything about risks/benefits except if it has a black box warning
- Help-Seeking Ads - can describe a condition and encourage discussion with doctor; can’t recommend specific drug treatment
Describe the major pieces of legislation pertaining to drugs in the US over the past century.
1) 1906 Pure Food and Drug Act - to prohibit mislabeling or adulteration of drugs
2) 1938 Food, Drug, and Cosmetic Act - required that new drugs be safe as well as pure
3) 1962 Amendment to Food, Drug, and Cosmetic Act - required that new drugs also be efficacious
What is a Herg channel assay?
Herg channels are potassium channels particularly in heart; assaying these channels is important for determining cardiogenic effects (like arrhythmias)
